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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2014

Open Access 01-12-2014 | Research article

Preventive effects of Chlorella on skeletal muscle atrophy in muscle-specific mitochondrial aldehyde dehydrogenase 2 activity-deficient mice

Authors: Yuya Nakashima, Ikuroh Ohsawa, Kiyomi Nishimaki, Shoichiro Kumamoto, Isao Maruyama, Yoshihiko Suzuki, Shigeo Ohta

Published in: BMC Complementary Medicine and Therapies | Issue 1/2014

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Abstract

Background

Oxidative stress is involved in age-related muscle atrophy, such as sarcopenia. Since Chlorella, a unicellular green alga, contains various antioxidant substances, we used a mouse model of enhanced oxidative stress to investigate whether Chlorella could prevent muscle atrophy.

Methods

Aldehyde dehydrogenase 2 (ALDH2) is an anti-oxidative enzyme that detoxifies reactive aldehydes derived from lipid peroxides such as 4-hydroxy-2-nonenal (4-HNE). We therefore used transgenic mice expressing a dominant-negative form of ALDH2 (ALDH2*2 Tg mice) to selectively decrease ALDH2 activity in the muscles. To evaluate the effect of Chlorella, the mice were fed a Chlorella-supplemented diet (CSD) for 6 months.

Results

ALDH2*2 Tg mice exhibited small body size, muscle atrophy, decreased fat content, osteopenia, and kyphosis, accompanied by increased muscular 4-HNE levels. The CSD helped in recovery of body weight, enhanced oxidative stress, and increased levels of a muscle impairment marker, creatine phosphokinase (CPK) induced by ALDH2*2. Furthermore, histological and histochemical analyses revealed that the consumption of the CSD improved skeletal muscle atrophy and the activity of the mitochondrial cytochrome c oxidase.

Conclusions

This study suggests that long-term consumption of Chlorella has the potential to prevent age-related muscle atrophy.
Appendix
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Literature
1.
Mecocci P, Fanó G, Fulle S, MacGarvey U, Shinobu L, Polidori MC, Cherubini A, Vecchiet J, Senin U, Beal MF: Age-dependent increases in oxidative damage to DNA, lipids, and proteins in human skeletal muscle. Free Radic Biol Med. 1999, 26: 303-308. 10.1016/S0891-5849(98)00208-1.CrossRefPubMed
2.
Pansarasa O, Bertorelli L, Vecchiet J, Felzani G, Marzatico F: Age-dependent changes of antioxidant activities and markers of free radical damage in human skeletal muscle. Free Radic Biol Med. 1999, 27: 617-622. 10.1016/S0891-5849(99)00108-2.CrossRefPubMed
3.
Lim PS, Cheng YM, Wei YH: Increase in oxidative damage to lipids and proteins in skeletal muscle of uremic patients. Free Radic Biol Med. 2002, 36: 295-301.CrossRef
4.
Gianni P, Jan KJ, Douglas MJ, Stuart PM, Tarnopolsky MA: Oxidative stress and the mitochondrial theory of aging in human skeletal muscle. Exp Gerontol. 2004, 39: 1391-1400. 10.1016/j.exger.2004.06.002.CrossRefPubMed
5.
Hamilton ML, van Remmen H, Drake JA, Yang H, Guo ZM, Kewitt K, Walter CA, Richardson A: Does oxidative damage to DNA increase with age?. Proc Natl Acad Sci U S A. 2001, 98: 10469-10474. 10.1073/pnas.171202698.CrossRefPubMedPubMedCentral
6.
Çakatay U, Telci A, Kayali R, Tekeli F, Akçay T, Sivas A: Relation of aging with oxidative protein damage parameters in the rat skeletal muscle. Clin Biochem. 2003, 36: 51-55. 10.1016/S0009-9120(02)00407-1.CrossRefPubMed
7.
Ohsawa I, Nishimaki K, Murakami Y, Suzuki Y, Ishikawa M, Ohta S: Age-dependent neurodegeneration accompanying memory loss in transgenic mice defective in mitochondrial aldehyde dehydrogenase 2 activity. J Neurosci. 2008, 28: 6239-6249. 10.1523/JNEUROSCI.4956-07.2008.CrossRefPubMed
8.
Endo J, Sano M, Katayama T, Hishiki T, Shinmura K, Morizane S, Matsuhashi T, Katsumata Y, Zhang Y, Ito H, Nagahata Y, Marchitti S, Nishimaki K, Wolf AM, Nakanishi H, Hattori F, Vasiliou V, Adachi T, Ohsawa I, Taguchi R, Hirabayashi Y, Ohta S, Suematsu M, Ogawa S, Fukuda K: Metabolic remodeling induced by mitochondrial aldehyde stress stimulates tolerance to oxidative stress in the heart. Circ Res. 2009, 105: 1118-1127. 10.1161/CIRCRESAHA.109.206607.CrossRefPubMed
9.
Conklin D, Prough R, Bhatanagar A: Aldehyde metabolism in the cardiovascular system. Mol Biosyst. 2007, 3: 136-150. 10.1039/b612702a.CrossRefPubMed
10.
Higuchi S, Matsushita S, Masaki T, Yokoyama A, Kimura M, Suzuki G, Mochizuki H: Influence of genetic variations of ethanolmetabolizing enzymes on phenotypes of alcohol-related disorders. Ann NY Acad Sci. 2004, 1025: 472-480. 10.1196/annals.1316.058.CrossRefPubMed
11.
Ohsawa I, Kamino K, Nagasaka K, Ando F, Niino N, Shimokata H, Ohta S: Genetic deficiency of a mitochondrial aldehyde dehydrogenase increases serum lipid peroxides in community-dwelling females. J Hum Genet. 2003, 48: 404-409. 10.1007/s10038-003-0046-y.CrossRefPubMed
12.
Kamino K, Nagasaka K, Imagawa M, Yamamoto H, Yoneda H, Ueki A, Kitamura S, Namekata K, Miki T, Ohta S: Deficiency in mitochondrial aldehyde dehydrogenase increases the risk for late-onset Alzheimer’s disease in the Japanese population. Biochem Biophys Res Commun. 2000, 273: 192-196. 10.1006/bbrc.2000.2923.CrossRefPubMed
13.
Suzuki Y, Muramatsu T, Taniyama M, Atsumi Y, Suematsu M, Kawaguchi R, Higuchi S, Asahina T, Murata C, Handa M, Mastuoka K: Mitochondrial aldehyde dehydrogenase in diabetes associated with mitochondrial tRNA(Leu(UUR)) mutation at position 3243. Diabetes Care. 1996, 19: 1423-1425. 10.2337/diacare.19.12.1423.CrossRefPubMed
14.
Yokoyama A, Muramatsu T, Ohmori T, Yokoyama T, Okuyama K, Takahashi H, Hasegawa Y, Higuchi S, Maruyama K, Shirakura K, Ishii H: Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics. Carcinogenesis. 1998, 19: 1383-1387. 10.1093/carcin/19.8.1383.CrossRefPubMed
15.
Takagi S, Baba S, Iwai N, Fukuda M, Katsuya T, Higaki J, Mannami T, Ogata J, Goto Y, Ogihara T: The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese but does not alter the sensitivity to pressor effects of alcohol: the Suita study. Hypertens Res. 2001, 24: 365-370. 10.1291/hypres.24.365.CrossRefPubMed
16.
Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D: Targeting aldehyde dehydrogenase2: new therapeutic opportunities. Physiol Rev. 2014, 94: 1-34. 10.1152/physrev.00017.2013.CrossRefPubMedPubMedCentral
17.
Ohsawa I, Nishimaki K, Yasuda C, Kamino K, Ohta S: Deficiency in a mitochondrial aldehyde dehydrogenase increases vulnerability to oxidative stress in PC12 cells. J Neurochem. 2003, 84: 1110-1117. 10.1046/j.1471-4159.2003.01619.x.CrossRefPubMed
18.
Ohta S, Ohsawa I, Kamino K, Ando F, Shimokata H: Mitochondrial ALDH2 deficiency as an oxidative stress. Ann NY Acad Sci. 2004, 1011: 36-44. 10.1196/annals.1293.004.CrossRefPubMed
19.
Rosenberg IH: Sarcopenia: origins and clinical relevance. J Nutr. 1997, 127: 990S-991S.PubMed
20.
Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R: The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc. 2004, 52: 80-85. 10.1111/j.1532-5415.2004.52014.x.CrossRefPubMed
21.
Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD: Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 2004, 147: 755-763.CrossRef
22.
Melton LJ, Khosla S, Crowson CS, O’Connor MK, O’Fallon WM, Riggs BL: Epidemiology of sarcopenia. J Am Geriatr Soc. 2000, 48: 625-630.CrossRefPubMed
23.
Weindruch R: Interventions based on the possibility that oxidative stress contributes to sarcopenia. J Gerontol A Biol Sci Med Sci. 1995, 50: 157-161.PubMed
24.
Schneider C, Tallman KA, Porter NA, Brash AR: Two distinct pathways of formation of 4-hydroxynonenal. Mechanisms of nonenzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals. J Biol Chem. 2001, 276: 20831-20838. 10.1074/jbc.M101821200.CrossRefPubMed
25.
Uchida K: 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog Lipid Res. 2003, 42: 318-343. 10.1016/S0163-7827(03)00014-6.CrossRefPubMed
26.
Hasegawa T, Kimura Y, Hiromastsu K, Kobayashi N, Yamada A, Makino M, Okuda M, Sano T, Nomoto K, Yoshikai Y: Effect of hot water extract of Chlorella vulgaris on cytokine expression patterns in mice with murine acquired immunodeficiency syndrome after infection with Listeria monocyto-genes. Immunopharmacology. 1997, 35: 273-282. 10.1016/S0162-3109(96)00150-6.CrossRefPubMed
27.
Konishi F, Tanaka K, Himeno K, Taniguti K, Nomoto K: Antitumor effect induced by a hot water extract of Chlorella vulgaris (CE): resistance to Meth-A tumor growth mediated by CE-induced polymorphonuclear leukocytes. Cancer Immunol Immunother. 1985, 19: 73-78.CrossRefPubMed
28.
Tanaka K, Koga T, Konishi F, Nakamura M, Mitsuyama M, Himeno K, Nomoto K: Augmentation of host defense by a unicellular green alga, Chlorella vulgaris, to Escherichia coli infection. Infect Immun. 1986, 53: 267-271.PubMedPubMedCentral
29.
Lee HS, Choi CY, Cho C, Song Y: Attenuating effect of chlorella supplementation on oxidative stress and NFkappaB activation in peritoneal macrophages and liver of C57BL/6 mice fed on an atherogenic diet. Biosci Biotechnol Biochem. 2003, 67: 2083-2090. 10.1271/bbb.67.2083.CrossRefPubMed
30.
Pratt R, Johnson E: Production of thiamine, riboflavin, folic acid, and biotin by Chlorella vulgaris and Chlorella pyrenoidosa. J Pharm Sci. 1965, 54: 871-874. 10.1002/jps.2600540611.CrossRefPubMed
31.
Shibata S, Natori Y, Nishihara T, Tomisaka K, Matsumoto K, Sansawa H, Nguyen VC: Antioxidant and anti-cataract effects of chlorella on rats with streptozotocin induced diabetes. J Nutr Sci Vitaminol (Tokyo). 2003, 49: 334-339. 10.3177/jnsv.49.334.CrossRef
32.
Makpol S, Yeoh TW, Ruslam FA, Arifin KT, Yusof YA: Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction on antioxidant enzymes activity in cellular ageing of human diploid fibroblasts. BMC Complement Altern Med. 2013, 13 (1): 1-10. 10.1186/1472-6882-13-1.CrossRef
33.
Aizzat O, Yap SW, Sopiah H, Madiha MM, Hazreen M, Shailah A, Wan JW, Nur SA, Srijit D, Musalmah M, Yasmin AM: Modulation of oxidative stress by Chlorella vulgaris in streptozotocin (STZ) induced diabetic Sprague–Dawley rats. Adv Med Sci. 2010, 55 (2): 281-288. 10.2478/v10039-010-0046-z.CrossRefPubMed
34.
Aliahmat NS, Noor MR, Yusof WJ, Makpol S, Ngah WZ, Yusof YA: Antioxidant enzyme activity and malondialdehyde levels can be modulated by Piper betle, tocotrienol rich fraction and Chlorella vulgaris in aging C57BL/6 mice. Clinics (Sao Paulo). 2012, 67 (12): 1147-1154.CrossRef
35.
Peng HY, Chu YC, Chen SJ, Chou ST: Hepatoprotection of chlorella against carbon tetrachloride-induced oxidative damage in rats. In Vivo. 2009, 23 (5): 747-754.PubMed
36.
Son YA, Shim JA, Hong S, Kim MK: Intake of Chlorella vulgaris improves antioxidative capacity in rats oxidatively stressed with dietary cadmium. Ann Nutr Metab. 2009, 54 (1): 7-14. 10.1159/000199453.CrossRefPubMed
37.
Vijayavel K, Anbuselvam C, Balasubramanian MP: Antioxidant effect of the marine algae Chlorella vulgaris against naphthalene-induced oxidative stress in the albino rats. Mol Cell Biochem. 2007, 303 (1–2): 39-44.CrossRefPubMed
38.
Kawasaki H, Sano T, Kaku E, Watanabe K, Kumamoto Y, Tanaka K: Toxicological study of chlorella. Acute and subacute toxicity in young rats by oral administration (in Japanese). Kurumeigakukaizasshi. 1977, 40 (11): 1510-1516.
39.
Nakashima Y, Ohsawa I, Konishi F, Hasegawa T, Kumamoto S, Suzuki Y, Ohta S: Preventive effects of Chlorella on cognitive decline in age-dependent dementia model mice. Neurosci Lett. 2009, 464: 193-198. 10.1016/j.neulet.2009.08.044.CrossRefPubMed
40.
Hasegawa T, Ito K, Ueno S, Kumamoto S, Ando Y, Yamada A, Nomoto K, Yasunobu Y: Oral administration of hot water extracts of Chlorella vulgaris reduces IgE production against milk casein in mice. Int J Immunopharmacol. 1999, 21 (5): 311-323. 10.1016/S0192-0561(99)00013-2.CrossRefPubMed
41.
Reeves PG, Nielsen FH, Fahey GC: AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet. J Nutr. 1993, 123: 1939-1951.PubMed
42.
McKenzie D, Bua E, McKiernan S, Cao Z, Aiken JM: Mitochondrial DNA deletion mutations: a causal role in sarcopenia. Eur J Biochem. 2002, 269: 2010-2015. 10.1046/j.1432-1033.2002.02867.x.CrossRefPubMed
43.
Semba RD, Lauretani F, Ferrucci L: Carotenoids as protection against sarcopenia in older adults. Arch Biochem Biophys. 2007, 458: 141-145. 10.1016/j.abb.2006.11.025.CrossRefPubMed
44.
Kruk J, Jemioła-Rzemińska M, Strzałka K: Plastoquinol and α-tocopherol quinol are more active than ubiquinol and α-tocopherol in inhibition of lipid peroxidation. Chem Phys Lipids. 1997, 87: 73-80. 10.1016/S0009-3084(97)00027-3.CrossRef
45.
Skulachev VP, Anisimov VN, Antonenko YN, Bakeeva LE, Chernyak BV, Erichev VP, Filenko OF, Kalinina NI, Kapelko VI, Kolosova NG, Kopnin BP, Korshunova GA, Lichinitser MR, Obukhova LA, Pasyukova EG, Pisarenko OI, Roginsky VA, Ruuge EK, Senin II, Severina II, Skulachev MV, Spivak IM, Tashlitsky VN, Tkachuk VA, Vyssokikh MY, Yaguzhinsky LS, Zorov DB: An attempt to prevent senescence: a mitochondrial approach. Biochim Biophys Acta. 2009, 1787: 437-461. 10.1016/j.bbabio.2008.12.008.CrossRefPubMed
46.
Hiona A, Leeuwenburgh C: The role of mitochondrial DNA mutations in aging and sarcopenia: implications for the mitochondrial vicious cycle theory of aging. Exp Gerontol. 2008, 43: 24-33. 10.1016/j.exger.2007.10.001.CrossRefPubMed
47.
Wanagat J, Cao Z, Pathare P, Aiken JM: Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. Faseb J. 2001, 15: 322-332. 10.1096/fj.00-0320com.CrossRefPubMed
48.
Cao Z, Wanagat J, McKiernan SH, Aiken JM: Mitochondrial DNA deletion mutations are concomitant with ragged red regions of individual, aged muscle fibers: analysis by laser-capture microdissection. Nucleic Acids Res. 2001, 29: 4502-4508. 10.1093/nar/29.21.4502.CrossRefPubMedPubMedCentral
49.
Bua EA, McKiernan SH, Wanagat J, McKenzie D, Aiken JM: Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia. J Appl Physiol. 2002, 92: 2617-2624.CrossRefPubMed
50.
Gokey NG, Cao Z, Pak JW, Lee D, McKiernan SH, McKenzie D, Weindruch R, Aiken JM: Molecular analyses of mtDNA deletion mutations in microdissected skeletal muscle fibers from aged rhesus monkeys. Aging Cell. 2004, 3: 319-326. 10.1111/j.1474-9728.2004.00122.x.CrossRefPubMed
51.
Bua E, Johnson J, Herbst A, Delong B, McKenzie D, Salamat S, Aiken JM: Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am J Hum Genet. 2006, 79: 469-480. 10.1086/507132.CrossRefPubMedPubMedCentral
52.
Herbst A, Pak JW, McKenzie D, Bua E, Bassiouni M, Aiken JM: Accumulation of mitochondrial DNA deletion mutations in aged muscle fibers: evidence for a causal role in muscle fiber loss. J Gerontol A Biol Sci Med Sci. 2007, 62: 235-245. 10.1093/gerona/62.3.235.CrossRefPubMedPubMedCentral
53.
Chen J, Schenker S, Frosto TA, Henderson GI: Inhibition of cytochrome c oxidase activity by 4-hydroxynonenal (HNE). Role of HNE adduct formation with the enzyme subunits. Biochim Biophys Acta. 1998, 1380: 336-344. 10.1016/S0304-4165(98)00002-6.CrossRefPubMed
54.
Paddon-Jones D, Short KR, Campbell WW, Volpi E, Wolfe RR: Role of dietary protein in the sarcopenia of aging. Am J Clin Nutr. 2008, 87: 1562S-1566S.PubMed
55.
Paddon-Jones D, Rasmussen BB: Dietary protein recommendations and the prevention of sarcopenia. Curr Opin Clin Nutr Care. 2009, 12: 86-90. 10.1097/MCO.0b013e32831cef8b.CrossRef
56.
Dreyer HC, Volpi E: Role of protein and amino acids in the pathophysiology and treatment of sarcopenia. J Am Coll Nutr. 2005, 24: 140S-145S. 10.1080/07315724.2005.10719455.CrossRefPubMedPubMedCentral
57.
Metadata
Title
Preventive effects of Chlorella on skeletal muscle atrophy in muscle-specific mitochondrial aldehyde dehydrogenase 2 activity-deficient mice
Authors
Yuya Nakashima
Ikuroh Ohsawa
Kiyomi Nishimaki
Shoichiro Kumamoto
Isao Maruyama
Yoshihiko Suzuki
Shigeo Ohta
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2014
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-14-390

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